We are studying the control of purine biosynthesis in liver under dietary conditions associated with different rates of de novo purine biosynthesis, polysome aggregation and ribonucleic acid (RNA) metabolism. These studies suggest the following: 1) The supply of amino acids regulates polysome aggregation and RNA breakdown and that the amino acids or some factor concerned with polysome aggregation and disaggregation regulates de novo purine biosynthesis. 2) The concentrations of substrates (phosphoribosyl pyrophosphate (PRPP) and glutamine) for the enzyme glutamine phosphoribosyl pyrophosphate amidotransferase (gln-PRPP amidotransferase) do not ordinarily regulate de novo purine biosynthesis. 3) Dietary adenine markedly affects the rate of de novo purine biosynthesis, as well as the relative activities of adenosine deaminase and adenine phosphoribosyl transferase. 4) The relative activities of purine interconverting enzymes, adenosine deaminase and adenosine kinase, appear to play a key role in regulating de novo biosynthesis of purines in the mammalian system. The objectives of this research program, therefore, are to continue the study of the control aspects of purine biosynthesis in liver and cultured human fibroblasts, and to elucidate the ways in which a defective regulation of these processes leads to gout. These objectives are necessary for an understanding of the way the mammal regulates the production of the relatively insoluble metabolite uric acid. Our approach is to study individual components of the purine synthesizing and interconverting machinery in liver of rats under dietary conditions known to have markedly different rates of purine biosynthesis. These investigations are also being supplemented with studies on cultured fibroblasts from normal as well as patients with clinical gout.